Gastric ulceration continues to be a major surgical problem due to the frequent inability to effectively manage this entity medically, its high recurrence rate after initial healing, and associated complications which often require operation. Directly related to this difficulty in nonsurgical management is our current lack of understanding gastric ulcer formation. Considerable evidence exists which indicates that prostaglandins can experimentally protect the gastric mucosa against a variety of noxious agents and promote healing of gastric ulcerations in man. This demonstration, coupled with the fact that these agents are abundantly distributed throughout the gastric mucosa of man and animals, suggests that they may serve a physiologic role in maintaining normal gastric musosal integrity. This grant proposal is aimed at increasing our understanding of the possible mechanisms whereby prostaglandins mediate their anti-ulcer effects and defining more clearly the role of endogenous prostaglandins in the pathogenesis of gastric mucosal ulceration. Mechanisms to be studied will include the effect of prostaglandins and gastric ulcerogens (i.e., aspirin, alcohol, and bile salts) on ionic permeability across the gastric mucosa; mucosal blood flow and oxygen consumption, intracellular cyclic nucleotide production; mucosal macromolecular (i.e., DNA, RNA, and protein) synthesis; and active ion transport. To assess the role of endogenous prostaglandins in the pathogenesis of gastric ulceration, the relationship between gastric injury and tissue levels of prostaglandins will be assessed by directly applying various damaging agents to the canine gastric mucosa and measuring changes in mucosal prostaglandin levels using both bioassay and immunoassay techniques. In addition, tissue slices from rat and dog gastric mucosa will be examined to determine whether specific receptors for prostaglandins exist in the gastric mucosa and what effect damaging agents have on altering the binding of prostaglandins to these putative receptors. These studies will hopefully help us understand more clearly the etiology of gastric ulceration and in turn provide a more solid basis for its prophylaxis and treatment.